AIMTo study the effects of yi-zhi II (a compond of Chinese Traditional Medicine) on the alteration of synaptic structure in hippocampal CA3 and maintenance of memoy.

METHODSBy using the method of oral administration of yi-zhi II, the step-through test and electron microscopy, the latency of step-through and synaptic structure in hippocamal CA3 were tested.

RESULTS(1) The mice which had been given yi-zhi II prolong significantly the latency of step through (P < 0.05 or P < 0.01) on the 1st, 6th and 12th day after learning. (2) On the 6th and 12th day after learning, the length of synaptic active zone were markly improved in yi-zhi II and control, but that of yi-zhi II was better than that of control. (On the 6th day after learning, the number of perforated synapses and axo-dendrite synapses were significantly improved by the yi-zhi II (P < 0.05).

CONCLUSIONThe yi-zhi II could improve the learning and memory in mice. It migth improve the memory by increasing the length of synaptic active zone and the number of perforated synapses and axo-dendrite synapses in hippocampal CA3.

Animals ; Avoidance Learning ; drug effects ; CA3 Region, Hippocampal ; drug effects ; physiology ; Chromosome Pairing ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Memory ; drug effects ; Mice ; Neuroprotective Agents ; pharmacology

OBJECTIVETo explore the effect of tetramethylpyrazine on learning, memory, and cholinergic system in D-galactose-lesioned mice.

METHODSC57BL/6J mice were given subcutaneous injection of 2% D-galactose for 40 days (100 mg.kg-1.d-1). Normal saline, tetramethylpyrazine (TMP) and Huperzine A (HupA) were given respectively by intragastric administration in different study groups from the third week on. Learning and memory ability were tested by Morris water maze for 5 days at the sixth week. Acetylcholinesterase (AchE) activity, the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor were determined.

RESULTSThe learning and memory dysfunction, with lowered AchE activity and M-cholinergic receptor binding sites were found in the model group as compared with the normal control group. The tetramethylpyrazine, especially at the dose of 100 mg.kg-1.d-1, could markedly attenuate cognitive dysfunction, while elevate the lowered AchE activity (P < 0.05) and M-cholinergic receptor binding sites (P < 0.005) in the cerebral cortex of mice treated with D-galactose.

CONCLUSIONSThe tetramethylpyrazine can significantly improve central cholinergic system function, and thus enhance the learning and memory ability in D-galactose-lesioned mice.

Acetylcholinesterase ; metabolism ; Animals ; Avoidance Learning ; drug effects ; Cognition ; drug effects ; Galactose ; Learning ; drug effects ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred C57BL ; Pyrazines ; pharmacology ; Receptor, Muscarinic M1 ; metabolism ; Receptors, Cholinergic ; drug effects ; physiology

OBJECTIVEPrevious studies have demonstrated that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain. But little is known if marginal vitamin A deficiency (MVAD) beginning from embryonic period affects the brain development and the ability of learning and memory in young rats. The aim of this study was to identify the effects of MVAD and vitamin A intervention (VAI) on learning, memory and the hippocampal CA1 long-term potentiation (LTP) in young rats.

METHODSRats were divided into control, MVAD and VAI groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 IU/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 IU/kg). In VAI group (9 young rats) the dams were fed with MVAD diet and the pups were fed with normal diet from postnatal week 4. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique and relative intensity of fluorescence in cells in hippocampal slices was measured by confocal laser scanning microscopy labeled by fluo-3.

RESULTS(1) The times to reach the learning standard in both VAI group (28.8 +/- 4.1) and MVAD group (45.6 +/- 12.1) were more than control group (17.1 +/- 4.4) (P < 0.01), and that of MVAD group was more than VAI group (P < 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group (22.9% +/- 9.4%) and VAI group (29.5% +/- 13.7%) were less than that of control group (57.5% +/- 27.3%), respectively (P < 0.01). No significant difference was found between VAI and MVAD groups (P > 0.05). (3) No significant differences of relative intensity of fluorescence in cells were found among the three groups before the tetanus stimulation. However, the significantly low relative intensity of fluorescence in cells was seen in MVAD (65.1 +/- 17.0) and VAI (85.8 +/- 17.1) groups compared with control group (113.6 +/- 20.5) after the tetanus stimulation (P < 0.01), and that of VAI group was higher than that of MVAD group (P < 0.05).

CONCLUSIONMVAD beginning from embryonic period impairs learning, memory and LTP in young rats. But the losses might not be reversible if the vitamin A supplementation is late especially missing the critical period of hippocampus development. According to the experimental data, it is speculated that vitamin A may modulate the influx of calcium ion to influence the LTP and lead to the change of learning and memory.

Animals ; Animals, Newborn ; Avoidance Learning ; drug effects ; CA1 Region, Hippocampal ; drug effects ; physiology ; Electrophysiology ; Female ; Long-Term Potentiation ; drug effects ; physiology ; Male ; Memory ; drug effects ; Pregnancy ; Rats ; Rats, Wistar ; Vitamin A ; pharmacology ; Vitamin A Deficiency ; drug therapy

LiCl at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the brain regions implicated in CTA formation. It has been reported that nitric oxide (NO) may play a role in CTA learning and LiCl increases both the synthesis and activity of NO synthase (NOS) in the brain. In this study, we examined the effect of central N omega-nitro-L- arginine methyl ester (L-NAME) on the brain c-Fos expression and CTA learning induced by lithium in rats. In the results, intracerebroventricular L-NAME given prior to lithium did not change either the lithium-induced CTA or c-Fos in the relevant brain regions. This suggests that the brain NO system may not be involved in the neuronal activation during lithium-induced CTA formation.
Animals ; Avoidance Learning/*drug effects/physiology ; Brain/*physiology ; Conditioning (Psychology) /*drug effects/physiology ; Immunohistochemistry ; Injections, Intraventricular ; Lithium/*pharmacology ; Male ; NG-Nitroarginine Methyl Ester/*pharmacology ; Nitric Oxide/physiology ; Proto-Oncogene Proteins c-fos/*analysis ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't ; Taste/*drug effects/physiology

Animals always seek rewards and the related neural basis has been well studied. However, what happens when animals fail to get a reward is largely unknown, although this is commonly seen in behaviors such as predation. Here, we set up a behavioral model of repeated failure in reward pursuit (RFRP) in Drosophila larvae. In this model, the larvae were repeatedly prevented from reaching attractants such as yeast and butyl acetate, before finally abandoning further attempts. After giving up, they usually showed a decreased locomotor speed and impaired performance in light avoidance and sugar preference, which were named as phenotypes of RFRP states. In larvae that had developed RFRP phenotypes, the octopamine concentration was greatly elevated, while tβh mutants devoid of octopamine were less likely to develop RFRP phenotypes, and octopamine feeding efficiently restored such defects. By down-regulating tβh in different groups of neurons and imaging neuronal activity, neurons that regulated the development of RFRP states and the behavioral exhibition of RFRP phenotypes were mapped to a small subgroup of non-glutamatergic and glutamatergic octopaminergic neurons in the central larval brain. Our results establish a model for investigating the effect of depriving an expected reward in Drosophila and provide a simplified framework for the associated neural basis.
Acetates ; pharmacology ; Animals ; Animals, Genetically Modified ; Avoidance Learning ; physiology ; Biogenic Amines ; metabolism ; Conditioning, Operant ; physiology ; Drosophila ; physiology ; Drosophila Proteins ; genetics ; metabolism ; Feeding Behavior ; drug effects ; physiology ; Instinct ; Larva ; physiology ; Locomotion ; drug effects ; genetics ; Nervous System ; cytology ; Neurons ; physiology ; Octopamine ; metabolism ; RNA Interference ; physiology ; Reward ; Statistics, Nonparametric ; Transcription Factors ; genetics ; metabolism